
Supporting information
![]() | Crystallographic Information File (CIF) https://doi.org/10.1107/S160053680704696X/lh2509sup1.cif |
![]() | Structure factor file (CIF format) https://doi.org/10.1107/S160053680704696X/lh2509Isup2.hkl |
CCDC reference: 667265
To a solution of racemic (+/-)-4-ClMA (8.4 g, 0.045 mol) in 72 ml me thanol, was gradually added (5.7 mL, 0.045 mol) R-PEA. A white crystalline solid appeared. The mixture was heated to 333 K using a water bath and the solid dissolved. The solution was then allowed to stand at 333 K for 30 minutes and subsequently cooled slowly to 295 K. After standing at 295 K for 60 minutes, the precipitate was collected and washed twice with methanol. The filtered precipitate was recrystallized in methanol to give the optically pure salt R-4-ClMA·R-PEA (3.1 g, 45% yield). X-ray quality crystals of R-4-ClMA·R-PEA were grown from iso-propanol solution by slow evaporation at room temperature.
All H atoms were positioned geometrically and constrained as riding atoms with C—H = 0.98 Å and Uiso(H) = 1.2Ueq(C) for methyne H atoms and C—H = 0.96 Å and Uiso(H) = 1.5Ueq(C) for methyl H atoms and C—H = 0.93 Å and Uiso(H) = 1.2Ueq(C) for aromatic H atoms and O—H = 0.82 Å and Uiso(H) = 1.5Ueq(C) for hydroxyl H atoms and N—H = 0.89 Å and Uiso(H) = 1.5Ueq(C) for amine H atoms.
Optically active (R)-4-Chloromandelic acid (R4-ClMA), being a significant chiral intermediate, has been widely used to synthesize many new pharmaceuticals (Adams et al., 2002). Huang et al. (2005) prepared (R)-4-ClMA by enantioselective degradation of racemates with newly isolated Pseudomonas putida. Yamaguchi et al. (2002) carried out the optical resolution of racemic organic acids using optically active 4-amino-2-methyl-butan-1-ol as a resolving agent in 2-propanol solvent. However, there are significant drawbacks among the above mentioned methods such as low yield and the high cost of resolving agents. Our lab is searching for economically feasible methods.
In the investigation of the optical resolution of racemic 4-Chloromandelic acid by (R)-Phenylethylamine, crystals of (R)-Phenylethylamine-(R)-4-Chloromandelic acid (R4-ClMA·R-PEA), were obtained from a methanol solution containing racemic 4-Chloromandelic acid and (R)-Phenylethylamine. Herein we present the structure of R4-ClMA·R-PEA showing the successful optical resolution. The crystal structure of the enantiomeric (S,S) analogue has previously been published (Kinbara et al., 2001).
The title complex consists of an ion pair; an amine cation and a carboxylate anion. The stereochemistry of each of the ions is successfully resolved (see: Flack parameter (Flack, 1983)) to be the R enantiomer. Three N—H atoms and a single O—H atom show close contacts to adjacent carboxylate O atoms. Thus, a two-dimensional network of H-bonding is observed. This presumably gives rise to the lower solubility of this product as compared to the S4-ClMA,R-PEA product. At present, we are attempting to grow single crystals of the S,R product.
For background information, see: Adams et al. (2002); Huang et al. (2005); Yamaguchi et al. (2002); Langkilde et al. (2002); Hu et al. (2004). The crystal structure of the S,S enantiomer is isomorphous (Kinbara et al., 2001).
Data collection: COLLECT (Nonius, 2001); cell refinement: DENZO-SMN (Otwinowski & Minor, 1997); data reduction: DENZO-SMN (Otwinowski & Minor, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL/PC (Sheldrick, 2001); software used to prepare material for publication: SHELXTL/PC (Sheldrick, 2001).
![]() | Fig. 1. The molecular structure of the title compound with 30% probability displacement ellipsoids and the atom labelling scheme. |
C8H12N+·C8H6ClO3− | F(000) = 648 |
Mr = 307.76 | Dx = 1.312 Mg m−3 |
Orthorhombic, P212121 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: P 2ac 2ab | Cell parameters from 23622 reflections |
a = 6.8848 (3) Å | θ = 2.0–27.5° |
b = 8.3979 (3) Å | µ = 0.25 mm−1 |
c = 26.9433 (10) Å | T = 296 K |
V = 1557.80 (11) Å3 | Rod, colourless |
Z = 4 | 0.40 × 0.13 × 0.05 mm |
Nonius KappaCCD diffractometer | 2731 independent reflections |
Radiation source: fine-focus sealed tube | 2086 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.055 |
φ scans, and ω scans with κ offsets | θmax = 25.0°, θmin = 2.9° |
Absorption correction: multi-scan from symmetry-related measurements (SORTAV; Blessing, 1995) | h = −8→8 |
Tmin = 0.838, Tmax = 0.988 | k = −9→9 |
18157 measured reflections | l = −32→20 |
Refinement on F2 | Hydrogen site location: inferred from neighbouring sites |
Least-squares matrix: full | H-atom parameters constrained |
R[F2 > 2σ(F2)] = 0.038 | w = 1/[σ2(Fo2) + (0.0425P)2 + 0.2438P] where P = (Fo2 + 2Fc2)/3 |
wR(F2) = 0.095 | (Δ/σ)max < 0.001 |
S = 1.03 | Δρmax = 0.15 e Å−3 |
2731 reflections | Δρmin = −0.19 e Å−3 |
193 parameters | Extinction correction: SHELXL97 (Sheldrick, 1997), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
0 restraints | Extinction coefficient: 0.0116 (19) |
Primary atom site location: structure-invariant direct methods | Absolute structure: Flack (1983), 1121 Friedel pairs |
Secondary atom site location: difference Fourier map | Absolute structure parameter: −0.07 (10) |
C8H12N+·C8H6ClO3− | V = 1557.80 (11) Å3 |
Mr = 307.76 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 6.8848 (3) Å | µ = 0.25 mm−1 |
b = 8.3979 (3) Å | T = 296 K |
c = 26.9433 (10) Å | 0.40 × 0.13 × 0.05 mm |
Nonius KappaCCD diffractometer | 2731 independent reflections |
Absorption correction: multi-scan from symmetry-related measurements (SORTAV; Blessing, 1995) | 2086 reflections with I > 2σ(I) |
Tmin = 0.838, Tmax = 0.988 | Rint = 0.055 |
18157 measured reflections |
R[F2 > 2σ(F2)] = 0.038 | H-atom parameters constrained |
wR(F2) = 0.095 | Δρmax = 0.15 e Å−3 |
S = 1.03 | Δρmin = −0.19 e Å−3 |
2731 reflections | Absolute structure: Flack (1983), 1121 Friedel pairs |
193 parameters | Absolute structure parameter: −0.07 (10) |
0 restraints |
Experimental. M·P. 469 K. The specific rotation was [α]20D = -48.5° (c=1, C2H5OH), determined using a WZZ-1S Digital Polarimeter; 1H-NMR (d6-DMSO/TMS): δ 1.41 (d, 3H, CH3), 4.29 (m, 1H, CHNH2), 4.53 (s, 1H, CHOH), 7.27–7.44 (m, 9H, C6H5 and C6H4Cl) measured using an AVANCE 500 MHz NMR (BRUKER). IR (KBr): 3301(m), 3036(s), 2535(m), 1610(s), 1576(s), 1531(s), 1383(s), 1193(m), 1072(s), 776(s), 705(s), 553(m), 478(m),446(m) measured using a NICOLET 5SXC. Elemental analysis: Calc'd for C16H18NO3Cl (FW 307.8) C: 62.40, H: 5.85, N: 4.55; Found C: 62.71, H: 6.26, N: 4.48 using a Elementar Vario EL. |
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes. |
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. |
x | y | z | Uiso*/Ueq | ||
Cl1 | 1.08733 (15) | 1.26848 (13) | −0.22906 (3) | 0.1093 (4) | |
C2 | 0.9516 (4) | 1.2426 (3) | −0.17511 (10) | 0.0619 (7) | |
C3 | 0.7898 (4) | 1.1480 (3) | −0.17627 (10) | 0.0661 (8) | |
H3A | 0.7535 | 1.0971 | −0.2055 | 0.079* | |
C4 | 0.6809 (4) | 1.1287 (3) | −0.13362 (9) | 0.0537 (6) | |
H4A | 0.5702 | 1.0653 | −0.1344 | 0.064* | |
C5 | 0.7339 (3) | 1.2022 (2) | −0.08997 (8) | 0.0403 (5) | |
C6 | 0.8988 (4) | 1.2948 (3) | −0.08991 (10) | 0.0530 (6) | |
H6A | 0.9373 | 1.3442 | −0.0606 | 0.064* | |
C7 | 1.0087 (4) | 1.3160 (3) | −0.13242 (11) | 0.0666 (8) | |
H7A | 1.1195 | 1.3792 | −0.1319 | 0.080* | |
C8 | 0.6149 (3) | 1.1803 (3) | −0.04321 (8) | 0.0427 (6) | |
H8A | 0.6380 | 1.2723 | −0.0216 | 0.051* | |
O9 | 0.4138 (2) | 1.1733 (2) | −0.05381 (6) | 0.0592 (5) | |
H9A | 0.3595 | 1.2511 | −0.0417 | 0.089* | |
C10 | 0.6798 (3) | 1.0312 (3) | −0.01565 (8) | 0.0392 (5) | |
O11 | 0.8499 (2) | 1.03549 (18) | 0.00208 (6) | 0.0487 (4) | |
O12 | 0.5668 (2) | 0.91601 (18) | −0.01150 (6) | 0.0516 (4) | |
N13 | 0.6696 (3) | 0.6352 (2) | 0.04075 (7) | 0.0461 (5) | |
H13A | 0.6670 | 0.7336 | 0.0285 | 0.069* | |
H13B | 0.5842 | 0.5749 | 0.0246 | 0.069* | |
H13C | 0.7881 | 0.5946 | 0.0371 | 0.069* | |
C14 | 0.4278 (4) | 0.7292 (3) | 0.10083 (10) | 0.0608 (7) | |
H14A | 0.4446 | 0.8374 | 0.0902 | 0.091* | |
H14B | 0.3895 | 0.7275 | 0.1351 | 0.091* | |
H14C | 0.3292 | 0.6793 | 0.0810 | 0.091* | |
C15 | 0.6183 (3) | 0.6394 (3) | 0.09474 (8) | 0.0455 (6) | |
H15A | 0.5985 | 0.5297 | 0.1060 | 0.055* | |
C16 | 0.7750 (3) | 0.7132 (3) | 0.12610 (9) | 0.0445 (6) | |
C17 | 0.8086 (4) | 0.6529 (3) | 0.17348 (9) | 0.0606 (7) | |
H17A | 0.7429 | 0.5622 | 0.1840 | 0.073* | |
C18 | 0.9392 (5) | 0.7270 (4) | 0.20491 (10) | 0.0721 (8) | |
H18A | 0.9602 | 0.6861 | 0.2365 | 0.087* | |
C19 | 1.0372 (4) | 0.8594 (4) | 0.18997 (11) | 0.0664 (8) | |
H19A | 1.1238 | 0.9094 | 0.2114 | 0.080* | |
C20 | 1.0075 (4) | 0.9186 (3) | 0.14321 (11) | 0.0634 (8) | |
H20A | 1.0755 | 1.0082 | 0.1328 | 0.076* | |
C21 | 0.8777 (4) | 0.8465 (3) | 0.11138 (9) | 0.0530 (7) | |
H21A | 0.8591 | 0.8880 | 0.0797 | 0.064* |
U11 | U22 | U33 | U12 | U13 | U23 | |
Cl1 | 0.1089 (8) | 0.1380 (9) | 0.0811 (6) | 0.0112 (7) | 0.0429 (5) | 0.0314 (6) |
C2 | 0.0596 (18) | 0.0677 (18) | 0.0583 (17) | 0.0094 (16) | 0.0110 (14) | 0.0151 (15) |
C3 | 0.076 (2) | 0.0736 (18) | 0.0484 (16) | −0.0007 (17) | 0.0007 (15) | −0.0050 (15) |
C4 | 0.0510 (15) | 0.0571 (15) | 0.0531 (15) | −0.0083 (13) | −0.0019 (14) | −0.0021 (13) |
C5 | 0.0368 (12) | 0.0369 (12) | 0.0471 (13) | 0.0010 (10) | −0.0021 (11) | 0.0029 (11) |
C6 | 0.0498 (15) | 0.0539 (14) | 0.0552 (15) | −0.0087 (13) | −0.0040 (13) | 0.0047 (12) |
C7 | 0.0532 (16) | 0.0677 (19) | 0.079 (2) | −0.0111 (14) | 0.0051 (16) | 0.0172 (16) |
C8 | 0.0373 (13) | 0.0398 (13) | 0.0509 (14) | 0.0030 (10) | −0.0009 (11) | −0.0044 (10) |
O9 | 0.0358 (9) | 0.0656 (11) | 0.0760 (12) | 0.0102 (9) | 0.0029 (9) | −0.0010 (9) |
C10 | 0.0379 (14) | 0.0408 (13) | 0.0390 (12) | 0.0012 (11) | 0.0021 (11) | −0.0069 (10) |
O11 | 0.0426 (10) | 0.0503 (9) | 0.0532 (10) | 0.0008 (8) | −0.0060 (8) | 0.0020 (7) |
O12 | 0.0429 (9) | 0.0430 (8) | 0.0690 (11) | −0.0065 (8) | −0.0004 (9) | 0.0057 (8) |
N13 | 0.0381 (11) | 0.0452 (11) | 0.0551 (12) | 0.0027 (9) | −0.0016 (9) | −0.0044 (9) |
C14 | 0.0422 (14) | 0.0654 (17) | 0.0749 (18) | 0.0017 (14) | 0.0066 (13) | −0.0155 (14) |
C15 | 0.0463 (14) | 0.0388 (12) | 0.0514 (14) | −0.0045 (11) | 0.0062 (12) | −0.0013 (11) |
C16 | 0.0396 (13) | 0.0439 (12) | 0.0501 (14) | 0.0039 (11) | 0.0051 (11) | −0.0029 (12) |
C17 | 0.0684 (18) | 0.0593 (15) | 0.0541 (16) | −0.0036 (15) | 0.0061 (14) | 0.0066 (14) |
C18 | 0.086 (2) | 0.080 (2) | 0.0507 (16) | 0.008 (2) | −0.0072 (16) | −0.0019 (15) |
C19 | 0.0624 (18) | 0.0704 (18) | 0.0664 (18) | 0.0044 (16) | −0.0123 (15) | −0.0148 (16) |
C20 | 0.0522 (17) | 0.0576 (16) | 0.080 (2) | −0.0091 (14) | −0.0056 (16) | −0.0010 (15) |
C21 | 0.0511 (16) | 0.0511 (14) | 0.0568 (15) | −0.0078 (14) | −0.0065 (13) | 0.0081 (12) |
Cl1—C2 | 1.742 (3) | N13—H13B | 0.8900 |
C2—C7 | 1.363 (4) | N13—H13C | 0.8900 |
C2—C3 | 1.369 (4) | C14—C15 | 1.521 (3) |
C3—C4 | 1.381 (4) | C14—H14A | 0.9600 |
C3—H3A | 0.9300 | C14—H14B | 0.9600 |
C4—C5 | 1.377 (3) | C14—H14C | 0.9600 |
C4—H4A | 0.9300 | C15—C16 | 1.504 (3) |
C5—C6 | 1.376 (3) | C15—H15A | 0.9800 |
C5—C8 | 1.514 (3) | C16—C21 | 1.383 (3) |
C6—C7 | 1.384 (4) | C16—C17 | 1.393 (3) |
C6—H6A | 0.9300 | C17—C18 | 1.383 (4) |
C7—H7A | 0.9300 | C17—H17A | 0.9300 |
C8—O9 | 1.415 (3) | C18—C19 | 1.361 (4) |
C8—C10 | 1.523 (3) | C18—H18A | 0.9300 |
C8—H8A | 0.9800 | C19—C20 | 1.370 (4) |
O9—H9A | 0.8200 | C19—H19A | 0.9300 |
C10—O12 | 1.247 (3) | C20—C21 | 1.378 (3) |
C10—O11 | 1.265 (3) | C20—H20A | 0.9300 |
N13—C15 | 1.497 (3) | C21—H21A | 0.9300 |
N13—H13A | 0.8900 | ||
C7—C2—C3 | 121.1 (3) | H13A—N13—H13C | 109.5 |
C7—C2—Cl1 | 119.6 (2) | H13B—N13—H13C | 109.5 |
C3—C2—Cl1 | 119.3 (2) | C15—C14—H14A | 109.5 |
C2—C3—C4 | 119.4 (3) | C15—C14—H14B | 109.5 |
C2—C3—H3A | 120.3 | H14A—C14—H14B | 109.5 |
C4—C3—H3A | 120.3 | C15—C14—H14C | 109.5 |
C5—C4—C3 | 120.9 (2) | H14A—C14—H14C | 109.5 |
C5—C4—H4A | 119.5 | H14B—C14—H14C | 109.5 |
C3—C4—H4A | 119.5 | N13—C15—C16 | 112.72 (19) |
C6—C5—C4 | 118.2 (2) | N13—C15—C14 | 108.7 (2) |
C6—C5—C8 | 120.9 (2) | C16—C15—C14 | 110.69 (18) |
C4—C5—C8 | 120.9 (2) | N13—C15—H15A | 108.2 |
C5—C6—C7 | 121.5 (2) | C16—C15—H15A | 108.2 |
C5—C6—H6A | 119.2 | C14—C15—H15A | 108.2 |
C7—C6—H6A | 119.2 | C21—C16—C17 | 118.2 (2) |
C2—C7—C6 | 118.9 (3) | C21—C16—C15 | 122.6 (2) |
C2—C7—H7A | 120.6 | C17—C16—C15 | 119.0 (2) |
C6—C7—H7A | 120.6 | C18—C17—C16 | 120.3 (3) |
O9—C8—C5 | 111.52 (18) | C18—C17—H17A | 119.8 |
O9—C8—C10 | 110.60 (18) | C16—C17—H17A | 119.8 |
C5—C8—C10 | 110.28 (18) | C19—C18—C17 | 120.6 (3) |
O9—C8—H8A | 108.1 | C19—C18—H18A | 119.7 |
C5—C8—H8A | 108.1 | C17—C18—H18A | 119.7 |
C10—C8—H8A | 108.1 | C18—C19—C20 | 119.6 (3) |
C8—O9—H9A | 109.5 | C18—C19—H19A | 120.2 |
O12—C10—O11 | 124.5 (2) | C20—C19—H19A | 120.2 |
O12—C10—C8 | 119.9 (2) | C19—C20—C21 | 120.7 (3) |
O11—C10—C8 | 115.61 (19) | C19—C20—H20A | 119.7 |
C15—N13—H13A | 109.5 | C21—C20—H20A | 119.7 |
C15—N13—H13B | 109.5 | C20—C21—C16 | 120.6 (2) |
H13A—N13—H13B | 109.5 | C20—C21—H21A | 119.7 |
C15—N13—H13C | 109.5 | C16—C21—H21A | 119.7 |
C7—C2—C3—C4 | 1.1 (4) | C5—C8—C10—O12 | −114.3 (2) |
Cl1—C2—C3—C4 | −179.3 (2) | O9—C8—C10—O11 | −169.88 (19) |
C2—C3—C4—C5 | −0.6 (4) | C5—C8—C10—O11 | 66.3 (2) |
C3—C4—C5—C6 | −0.3 (4) | N13—C15—C16—C21 | 40.7 (3) |
C3—C4—C5—C8 | −179.7 (2) | C14—C15—C16—C21 | −81.2 (3) |
C4—C5—C6—C7 | 0.7 (3) | N13—C15—C16—C17 | −144.3 (2) |
C8—C5—C6—C7 | −179.9 (2) | C14—C15—C16—C17 | 93.7 (3) |
C3—C2—C7—C6 | −0.7 (4) | C21—C16—C17—C18 | 1.1 (4) |
Cl1—C2—C7—C6 | 179.7 (2) | C15—C16—C17—C18 | −174.1 (2) |
C5—C6—C7—C2 | −0.2 (4) | C16—C17—C18—C19 | −0.3 (4) |
C6—C5—C8—O9 | 143.6 (2) | C17—C18—C19—C20 | −0.7 (4) |
C4—C5—C8—O9 | −37.0 (3) | C18—C19—C20—C21 | 0.8 (4) |
C6—C5—C8—C10 | −93.1 (2) | C19—C20—C21—C16 | 0.1 (4) |
C4—C5—C8—C10 | 86.3 (3) | C17—C16—C21—C20 | −1.0 (4) |
O9—C8—C10—O12 | 9.6 (3) | C15—C16—C21—C20 | 174.0 (2) |
D—H···A | D—H | H···A | D···A | D—H···A |
O9—H9A···O11i | 0.82 | 2.09 | 2.848 (2) | 154 |
N13—H13A···O12 | 0.89 | 2.00 | 2.836 (2) | 157 |
N13—H13B···O11ii | 0.89 | 1.99 | 2.869 (3) | 167 |
N13—H13C···O12iii | 0.89 | 2.04 | 2.878 (3) | 156 |
Symmetry codes: (i) x−1/2, −y+5/2, −z; (ii) x−1/2, −y+3/2, −z; (iii) x+1/2, −y+3/2, −z. |
Experimental details
Crystal data | |
Chemical formula | C8H12N+·C8H6ClO3− |
Mr | 307.76 |
Crystal system, space group | Orthorhombic, P212121 |
Temperature (K) | 296 |
a, b, c (Å) | 6.8848 (3), 8.3979 (3), 26.9433 (10) |
V (Å3) | 1557.80 (11) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.25 |
Crystal size (mm) | 0.40 × 0.13 × 0.05 |
Data collection | |
Diffractometer | Nonius KappaCCD |
Absorption correction | Multi-scan from symmetry-related measurements (SORTAV; Blessing, 1995) |
Tmin, Tmax | 0.838, 0.988 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 18157, 2731, 2086 |
Rint | 0.055 |
(sin θ/λ)max (Å−1) | 0.595 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.038, 0.095, 1.03 |
No. of reflections | 2731 |
No. of parameters | 193 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.15, −0.19 |
Absolute structure | Flack (1983), 1121 Friedel pairs |
Absolute structure parameter | −0.07 (10) |
Computer programs: COLLECT (Nonius, 2001), DENZO-SMN (Otwinowski & Minor, 1997), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), SHELXTL/PC (Sheldrick, 2001).
D—H···A | D—H | H···A | D···A | D—H···A |
O9—H9A···O11i | 0.82 | 2.09 | 2.848 (2) | 154.3 |
N13—H13A···O12 | 0.89 | 2.00 | 2.836 (2) | 156.9 |
N13—H13B···O11ii | 0.89 | 1.99 | 2.869 (3) | 167.2 |
N13—H13C···O12iii | 0.89 | 2.04 | 2.878 (3) | 156.4 |
Symmetry codes: (i) x−1/2, −y+5/2, −z; (ii) x−1/2, −y+3/2, −z; (iii) x+1/2, −y+3/2, −z. |
Optically active (R)-4-Chloromandelic acid (R4-ClMA), being a significant chiral intermediate, has been widely used to synthesize many new pharmaceuticals (Adams et al., 2002). Huang et al. (2005) prepared (R)-4-ClMA by enantioselective degradation of racemates with newly isolated Pseudomonas putida. Yamaguchi et al. (2002) carried out the optical resolution of racemic organic acids using optically active 4-amino-2-methyl-butan-1-ol as a resolving agent in 2-propanol solvent. However, there are significant drawbacks among the above mentioned methods such as low yield and the high cost of resolving agents. Our lab is searching for economically feasible methods.
In the investigation of the optical resolution of racemic 4-Chloromandelic acid by (R)-Phenylethylamine, crystals of (R)-Phenylethylamine-(R)-4-Chloromandelic acid (R4-ClMA·R-PEA), were obtained from a methanol solution containing racemic 4-Chloromandelic acid and (R)-Phenylethylamine. Herein we present the structure of R4-ClMA·R-PEA showing the successful optical resolution. The crystal structure of the enantiomeric (S,S) analogue has previously been published (Kinbara et al., 2001).
The title complex consists of an ion pair; an amine cation and a carboxylate anion. The stereochemistry of each of the ions is successfully resolved (see: Flack parameter (Flack, 1983)) to be the R enantiomer. Three N—H atoms and a single O—H atom show close contacts to adjacent carboxylate O atoms. Thus, a two-dimensional network of H-bonding is observed. This presumably gives rise to the lower solubility of this product as compared to the S4-ClMA,R-PEA product. At present, we are attempting to grow single crystals of the S,R product.